Miotto 2020 Am J Physiol Endocrinol Metab

[[Has title::Miotto PM, Petrick HL, Holloway GP (2020) Acute insulin deprivation results in altered mitochondrial substrate sensitivity conducive to greater fatty acid transport. Am J Physiol Endocrinol Metab [Epub ahead of print].]]

» [[Has info::PMID: 32543943]]

Was written by::Miotto PM, Was written by::Petrick HL, Was written by::Holloway GP (Was published in year::2020) Was published in journal::Am J Physiol Endocrinol Metab

Abstract: [[has abstract::Type 1 and type 2 diabetes are both tightly associated with impaired glucose control. While both pathologies stem from different mechanisms, a reduction in insulin action coincides with drastic metabolic dysfunction in skeletal muscle and metabolic inflexibility. However, the underlying explanation for this response remains poorly understood, particularly since it is difficult to distinguish the role of attenuated insulin action from the detrimental effects of reactive lipid accumulation which impair mitochondrial function and promote reactive oxygen species (ROS) emission. We therefore utilized streptozotocin to examine the effects of acute insulin deprivation, in the absence of a high lipid / nutrient excess environment, on the regulation of mitochondrial substrate sensitivity and ROS emission. The ablation of insulin resulted in reductions in absolute mitochondrial oxidative capacity, ADP-supported respiration, and reduced the ability for malonyl-CoA to inhibit carnitine palmitoyl-transferase I (CPT-I) and suppress fatty acid-supported respiration. These bioenergetic responses coincided with increased mitochondrial derived H₂O₂ emission and lipid transporter content, independent of major mitochondrial substrate transporter proteins and enzymes involved in fatty acid oxidation. Together, these data suggest that attenuated/ablated insulin signalling does not affect mitochondrial ADP sensitivity, while the increased reliance on fatty acid oxidation in situations where insulin action is reduced may occur as a result of altered regulation of mitochondrial fatty acid transport through CPT-I.]] • Keywords: has publicationkeywords::ADP sensitivity, has publicationkeywords::Insulin, has publicationkeywords::Lipid metabolism, has publicationkeywords::Mitochondria, has publicationkeywords::Streptozotocin • Bioblast editor: [[has editor::Plangger M]] • O2k-Network Lab: Was published by MiPNetLab::CA Guelph Holloway GP

Labels: MiParea: MiP area::Respiration  Pathology: Diseases::Diabetes 

Organism: Organism::Rat  Tissue;cell: tissue and cell::Skeletal muscle  Preparation: Preparation::Permeabilized tissue  Enzyme: Enzyme::Complex I, Enzyme::Complex II;succinate dehydrogenase, Enzyme::Complex III, Enzyme::Complex IV;cytochrome c oxidase, Enzyme::Complex V;ATP synthase 

Coupling state: Coupling states::LEAK, Coupling states::OXPHOS  Pathway: Pathways::F, Pathways::N, Pathways::NS  HRR: Instrument and method::Oxygraph-2k